GB2350297A - Injectable halogenated anesthetic formulation in emulsion form - Google Patents
Injectable halogenated anesthetic formulation in emulsion form Download PDFInfo
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- GB2350297A GB2350297A GB9912446A GB9912446A GB2350297A GB 2350297 A GB2350297 A GB 2350297A GB 9912446 A GB9912446 A GB 9912446A GB 9912446 A GB9912446 A GB 9912446A GB 2350297 A GB2350297 A GB 2350297A
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- 239000000203 mixture Substances 0.000 title claims abstract description 93
- 238000009472 formulation Methods 0.000 title claims abstract description 92
- 230000003444 anaesthetic effect Effects 0.000 title claims abstract description 67
- 239000000839 emulsion Substances 0.000 title abstract description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000007957 coemulsifier Substances 0.000 claims abstract description 17
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229960002725 isoflurane Drugs 0.000 claims abstract description 14
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 12
- 239000000787 lecithin Substances 0.000 claims abstract description 12
- 229940067606 lecithin Drugs 0.000 claims abstract description 12
- 235000010445 lecithin Nutrition 0.000 claims abstract description 12
- -1 for example Polymers 0.000 claims abstract description 11
- 235000012424 soybean oil Nutrition 0.000 claims abstract description 10
- 239000003549 soybean oil Substances 0.000 claims abstract description 10
- 238000002347 injection Methods 0.000 claims abstract description 9
- 239000007924 injection Substances 0.000 claims abstract description 9
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229920001993 poloxamer 188 Polymers 0.000 claims abstract description 8
- 229940044519 poloxamer 188 Drugs 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229960002078 sevoflurane Drugs 0.000 claims abstract description 6
- DFEYYRMXOJXZRJ-UHFFFAOYSA-N sevoflurane Chemical compound FCOC(C(F)(F)F)C(F)(F)F DFEYYRMXOJXZRJ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229920001400 block copolymer Polymers 0.000 claims abstract description 5
- 229960000305 enflurane Drugs 0.000 claims abstract description 4
- JPGQOUSTVILISH-UHFFFAOYSA-N enflurane Chemical compound FC(F)OC(F)(F)C(F)Cl JPGQOUSTVILISH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960003132 halothane Drugs 0.000 claims abstract description 4
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960003537 desflurane Drugs 0.000 claims abstract description 3
- DPYMFVXJLLWWEU-UHFFFAOYSA-N desflurane Chemical compound FC(F)OC(F)C(F)(F)F DPYMFVXJLLWWEU-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002671 adjuvant Substances 0.000 claims description 10
- 238000004945 emulsification Methods 0.000 claims description 10
- 229920001577 copolymer Polymers 0.000 claims description 9
- 239000003983 inhalation anesthetic agent Substances 0.000 claims description 8
- 229920001451 polypropylene glycol Polymers 0.000 claims description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000003995 emulsifying agent Substances 0.000 abstract description 14
- 238000009835 boiling Methods 0.000 abstract description 3
- 239000008346 aqueous phase Substances 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000010979 pH adjustment Methods 0.000 abstract 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- 229940035674 anesthetics Drugs 0.000 description 3
- 239000003193 general anesthetic agent Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 2
- 229960002455 methoxyflurane Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 2
- 229960004134 propofol Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 241000518994 Conta Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000003421 short acting drug Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/02—Halogenated hydrocarbons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/08—Ethers or acetals acyclic, e.g. paraformaldehyde
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Oncology (AREA)
- Anesthesiology (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An injectable anaesthetic formulation comprises a halogenated anaesthetic compound, such as desflurane, isoflurane, enflurane, halothane or sevoflurane, but preferably isoflurane, and at least one emulsifier, preferably soybean oil. Although not essential, it is preferred to also include lecithin (an emulsifier also) and a co-emulsifier such as a polyoxyethylene-polyoxypropylene block copolymer, for example, poloxamer 188. The composition may further contain water, a pH adjustment agent, such as sodium hydroxide, and/or glycerol. It is preferred that the halogenated anaesthetic has a boiling point between 20{ and 60{C. An example of such a formulation comprises isoflurane (10 ml); soybean oil (10 ml); glycerol (2.5 g), lecithin (1.8 g) and water (q.s.). The proportion of anaesthetic to emulsifier should be, at a minimum, 1 part emulsifier to 3 parts anaesthetic in order to ensure the formation of a stable emulsion. The total amount of dispersed non-aqueous phase (anaesthetic plus emulsifier(s)) should be less than or equal to about 32% v/v in order to provide a solution of suitable viscosity for administration by injection.
Description
2350297 -I- - INJECTABLE ANESTHETIC FORMULATION
Technical Field-of the Inynenticm
The field of the present invention is anesthetics. More particularly, this invention pertains to an injectable anesthetic formulation.
Aackgxajund -of the lLnnatlan Inhalation anesthetics such as isoflurane and sevoflurane are commonly used for anesthetizing patients for medical procedures. Although inhalation anesthetics are suitable for many medical procedures, they do have certain disadvantages. For example, induction of anesthesia by inhalation can be relatively sl6w in some patients. Further, the use of inhalation anesthetics requires the patient to breathe the anesthetic using a gas containment mask. The wearing of such a containment mask can be upsetting for some patients, is particularly children. For these and other reasons, rapid anesthetic induction is commonly performed by intravenous injection using relatively short acting agents such as propofol. Inhalation anesthetics are then used to maintain the anesthetized condition.
Inhalation anesthetics such as isoflurane and sevoflurane generally have been deemed unsuitable for parenteral administration due to -their low aqueous solubility, thereby making it difficult to formulate them for intravenous administration, i.e., their low solubility results in unacceptably large dose volumes.
The need for a suitable formulation for injection has been recognized in the art. For example, U.S. Patent No. 5,637,625 discloses a phospholipid coated, microdroplet propofol formulation. The disclosed formulation is devoid of fats and triglycerides so that the formulation provides sedation without fat overload. In addition, the formulation is free of nutrients capable of supporting bacterial growth, thereby providing the formulations with an increased shelf life. In addition, the use of lecithin-coated microdroplets of methoxyflurane was described in 'Tharmacokineties of Methoxyflurane After its Intra-dermal Injection as Lecithin-coated.Nficrodroplets," published in J. Controlled Release (1989), 9(l), 1 - 12. However, neither of these disclosures suggests the possibility of using an emulsion formulation of an inhalation anesthetic. 5 Sunirnary aLth-e-Umentign
The present invention is directed to an injectable anesthetic formulation. In a first embodiment of the present invention, the formulation contains a halogenated anesthetic in an amount not greater than approximately 24% v1v of the formulation and an emulsification adjuvant in an amount from approximately 8% to approximately 32% v/v of the formulation.-The formulation further contains lecithin in an amount from approximately 1.2% to approximately 2.4% w/v of the formulation and a co-emulsifier in an amount not greater than approximately 1% w/v of the formulation.
DetaflgdjDgeAgdation of theJUmenlion Although the present invention has been described herein in connection with certain exemplary and preferred embodiments, it will be appreciated by one of ordinary skill that various modifications can be made to the invention without departing from the scope of the invention, such scope being defined by the appended claims, The anesthetic formulations of the present invention have use in inducing maintaining anesthesia in humans and animals. The formulations include a halogenated volatile anesthetic having a boiling point between approximately 20' and approximately 60' C. Such halogenated volatile anesthetics include, but are not necessarily limited to, desflurane, isoflurane, enflurane, halothane, and sevoflurane. Each of these anesthetics is well-known in the art. Although the examples set forth herein disclose formulations containing isoflurane, it is to be understood that any halogenated anesthetic having the desired boiling point can be used in the formulations of the present invention.
The formulations of the present invention further include an emulsification adjuvant such as soybean oil. Those of ordinary skill in the art will appreciate that other emulsification adjuvants having the characteristics of soybean oil can be used without departing from the spirit and scope of the present invention.
It has been found that a minimum ratio of 1 part emulsification adjuvant to 3 parts anesthetic is required in order to provide a stable emulsion. Further, it has been found preferable to provide an anesthetic formulation in which the total volume of dispersed phase, i.e., anesthetic and emulsification adjuvant, in the anesthetic formulation is below approximately 32% v/v in order to ensure that the viscosity of the resulting anesthetic formulation is acceITtable for injection. In a preferred embodiment of the anesthetic formulation of the present invention, the halogenated anesthetic is present in an amount not greater than approximately 24% v/v while the emulsification adjuvant is present in an amount between approximately 8% and approximately 82% v/v.
The anesthetic formulation of the present invention further includes an emulsifier such as lecithin. Those of ordinary skill in the art will appreciate that other emulsifiers having the characteristics of lecithin can be used without departing from the spirit and scope of the present invention. The emulsifier is preferably present in an amount between approximately 0.6%_ and approximately 2.4% wtv. It has been found that emulsifier levels between approximately 1.2% and approximately 2.4% w1v are more preferable, and that emulsifier levels between approximately 1.8% and approximately 2.4% are most preferable in connection with the anesthetic formulation of the present invention, The anesthetic formulation of the present invention further includes a co.
emulsifier. An example of a co-emulsifier useful in connection with the anesthetic formulation of the present invention is a polyoxypropylene/polyoxyet,hylene block copolymer having a formula HO(C2H40)b(CaH60),(C2H40)bH where a is an integer such that a molecular weight represented by a polyoxypropylene portion of the copolymer is between approximately 900 to 15000, and b is an integer such that a molecular weight represented by a polyoxyethylene portion of the copolymer constitutes between approximately 5% and 90% of the copolymer. Those of ordinary skill in the art will appreciate that other co-emulsifiers having the characteristics of a polyoxypropylene/polyoxyethylerLe block copolymer can be used without departing from the spirit and scope of the present invention. In one embodiment of the present invention, poloxamer 188 is used as a co-emulsifier. The co emulsifier is preferably present in an amount not greater than approximately 1% wtv, as explained in greater detail below, and more preferably in an amount not greater than approximately 0.96%.
It has been discovered that at a total emulsifier lever (i.e-., emulsifier content plus co-emulsifier content) of 1,8% w/v, a ratio of 8 parts of lecithin to 2 parts of poloxamer 188 provided desirable results in a 20% v1v isoflurane formulation due to an apparent reduction in droplet size and an increased resistance to creaming, Creaming is a form of emulsion instability well known in the art. However, it has been discovered that no stability benefits are obtained by the inclusion of poloxamer 188 in a 10% v/v isoflurane formulation.
Accordingly, certain formulations in accordance with the present invention need not include a co-emulsifier such as poloxamer 188, Accordingly, as used herein, the term 'in an amount not greater than" is intended to include the complete absence of a co-emulsifier from the anesthetic formulation of the present invention, The anesthetic formulation of the present invention may further include a tonicifier such as glycerol. The tonicifter is used to adjust the tonicity of the anesthetic formulation to the tonicity of the patienVs blood plasma. In a preferred embodiment of the anesthetic formulation of the present invention, the tonicifier is present in an amount between approximately 1% and approximately 4% of the formulation.
The anesthetic formulation of the present invention may also include a pH adjustor in an amount sufficient to adjust the pH of the formulation to between approximately 6 and approximately 9, thereby making it suitable for injection and also for optimizing the stability of the emulsifier. A variety of known pH adjustors such as sodium hydroxide can be used in connection with the formulation of the present invention.
The preferred anesthetic formulation of the present invention further includes a vehicle for injection in a quantity sufficient for injection of the anesthetic formulation. Water can be used as the vehicle for injection The following examples are provided for the purpose of providing a further understanding of the anesthetic formulations of the present invention and are not intended to be limiting of the invention claimed in the appended claims.
EXaMRIC-1; A 10% v/v formulation of isoflurane was prepared. Each 100 ml of the resulting anesthetic formulation contained:
is isoflurane 10 ml soybean oil 10 mi glycerol 2.5 g lecithin 1.8 g distilled water q.s.
The soybean oil used in this example was winterized.
Ex=Rle 2:
A 20% v/v formulation of isoflurane was prepared. Each 100 ml of the resulting anesthetic formulation conta ined; isoflurane 20 ml soybean oil 10 MI glycerol 2.5 g lecithin 1.6 rng poloxamer 188 0.18 g distilled water q.s.
The soybean oil used in this example also was winterized, A pH adjustor (0.1 M sodium hydroxide) was added to adjust the pH of the resulting anesthetic formulation to between approximately 8 and approximately 9 prior to autoclaving of the resulting formulation.
Anesthetic formulations prepared in accordance with the present invention are suitable for terminal sterilization by autoclaving, e.g., heating to a temperature of approximately 121 C for approximately 15 minutes. This characteristic of the anesthetic formulations of the present inventions obviates the need for sterile processing, Although the present invention has been described herein in conjunction with certain preferred embodiments and examples, it win be appreciated that certain modifications to the anesthetic formulation of the present invention can be made without departing from the intended spirit and scope of the present invention which is defted by the appended claims.
Claims (22)
1. An injectable anesthetic formulation comprising: a halogenated volatile anesthetic in an amount not greater than approximately 24% v/v of said formulation; an emulsification adjuvant in an amount from approximately 8% to approximately 32% v/v of said formulation; lecithin in an amount from approximately 1.2% to approximately 2.4% w/v of said formulation; and a co-emulsifier in an amount not greater than approximately 1% w/v of said formulation.
2. Am injectable anesthetic formulation in accordance with Claim 1, wherein said halogenated anesthetic is selected from a group consisting of desflurane, isoflurane, enflurane, halothane, and sevoflurane.
3. An injectable anesthetic formulation in accordance with Claim 1, wherein said halogenated anesthetic is isaflurane.
4. An injectable, anesthetic formulation in accordance with Claim 1, wherein said co-emulsifier is a polyoxypropylene/polyoxyethylene block copolymer.
S. An injectable anesthetic formulation in accordance with Claim 4, wherein said co-emulsifier is poloxamer 188.
6. An injectable anesthetic formulation in accordance with Claim 4, wherein said co-emulsifier has a formula:
HO(C21140MCX80MC21,400 wherein a is an integer such that molecular weight represented by a polyoxypropylene portion of said copolymer is between approximately 900 to 15000, and b is an integer such that a molecular weight represented by a polyoxyethylene portion of said copolymer constitutes between approximately 5% and 90% of said copolymer.
7. An injectable anesthetic formulation in accordance with Claim 1, wherein said emulsification adjuvant is soybean oil,
S. An injectable anesthetic formulation in accordance with Claim 1, wherein said formulation further comprises glycerol in ail amount of between approximately 1% to approximately 4% w/v of said forriiWation.
9. An injectable anesthetic formulation in accordance with Claim 1, wherein said formulation further comprises water.
10. An injectable anesthetic formulation in accordance with Claim 1, wherein said formulation further comprises a pH adjustor.
11. An injectable anesthetic formulation in accordance with Claim 10, wherein said pH adjustor is sodium hydroxide,
12. An injectable anesthetic formulation comprising: a halogenated anesthetic in an amount not greater than approNimately 24% v/v of said formulation; an emulsification adjuvant in an amount from approximately 8% to approximately 32% v/v of said formulation; lecithin in an amount from approximately 1,2% to approximately 2.4% w/v of said formulation; and a co-emulsifier in an amount not greater than approximately 1% w/v of said formulation; 19- a quantity of glycerol; and a quantity of a pH adjustor sufficient to adjust a pH of said formulation to between approximately 6 and apprwdmately 9.
13, An injectable anesthetic formulation in accord-ance with Claim 12, wherein said halogenated anesthetic is selected from a group consisting of isaflurane, enflurane, halothane, and sevoflurane.
14. An injectable anesthetic formulation in accordance with Claim 12, wherein said halogenated anesthetic is isoilurane.
15. An injectable anesthetic formulation in accordance with Claim 1, wherein said co-emulsifier is a polyoxypropylene/polyoxyethylene block copolymer.
16. An injectable anesthetic formulation in accordance with Claim 15, wherein said co-emulsifier is poloxamer 188.
17. An injectable anesthetic formulation in accordance with Claim 15, wherein said co-emulsifier has a formula:
HO(C2H40)'b(C8H60)lk(C2I-I40)1,H wherein a is an integer such that molecular weight represented by a polyoxypropylene portion of said copolymer is between approximately 900 to 15000, and b, is an integer such that a molecular weight represented by a polyoxyethylene portion of said copolymer constitutes between approximately 5% and 90% of said copolymer.
18. An injectable anesthetic formulation in accordance with Claim 12, wherein said emulsification adjuvant is soybean oil.
19. An injectable anesthetic formulation in accordance with Claim 12, wherein glycerol is present in an amount of between approximately 1% to approximately 4% w/v of said formulation.
20. An injectable anesthetic formulation in accordance with Claim 1, wherein said formulation further comprises water in an amount sufficient for injection of said formulation
21. An injectable anesthetic formulation in accordance with Clairn 12, wherein said pH adjustor is sodium hydroNide,
22. An injectable anesthetic formulation substantially as herein described.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9912446A GB2350297A (en) | 1999-05-27 | 1999-05-27 | Injectable halogenated anesthetic formulation in emulsion form |
| PCT/US2000/014502 WO2000072820A2 (en) | 1999-05-27 | 2000-05-25 | Injectable anesthetic formulation |
| AU52926/00A AU5292600A (en) | 1999-05-27 | 2000-05-25 | Injectable anesthetic formulation |
| JP2000620932A JP2003520769A (en) | 1999-05-27 | 2000-05-25 | Injectable anesthetic preparations |
| EP00937799A EP1180014A2 (en) | 1999-05-27 | 2000-05-25 | Injectable anesthetic formulation |
| CA002371033A CA2371033A1 (en) | 1999-05-27 | 2000-05-25 | Injectable anesthetic formulation |
| US11/035,935 US20050129754A1 (en) | 1999-05-27 | 2005-01-14 | Injectable anesthetic formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9912446A GB2350297A (en) | 1999-05-27 | 1999-05-27 | Injectable halogenated anesthetic formulation in emulsion form |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB9912446D0 GB9912446D0 (en) | 1999-07-28 |
| GB2350297A true GB2350297A (en) | 2000-11-29 |
Family
ID=10854344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9912446A Withdrawn GB2350297A (en) | 1999-05-27 | 1999-05-27 | Injectable halogenated anesthetic formulation in emulsion form |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20050129754A1 (en) |
| EP (1) | EP1180014A2 (en) |
| JP (1) | JP2003520769A (en) |
| AU (1) | AU5292600A (en) |
| CA (1) | CA2371033A1 (en) |
| GB (1) | GB2350297A (en) |
| WO (1) | WO2000072820A2 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002094221A1 (en) * | 2001-05-18 | 2002-11-28 | Jupitar Pty Ltd | Emulsion and dispersion formulations and method |
| EP1558226A4 (en) * | 2002-10-11 | 2008-04-02 | Baxter Int | Method for cardioprotection and neuroprotection by intravenous administration of halogenated volatile anesthetics |
| EP2345427A1 (en) * | 2010-01-14 | 2011-07-20 | SapioTec GmbH | Fluoran complex |
| US9827394B2 (en) | 2011-09-21 | 2017-11-28 | University College Cardiff Consultants Limited | Dispersion anaesthetic device |
| US9925274B2 (en) | 2012-11-15 | 2018-03-27 | Sapiotec Gmbh | Delphinidin complex as an antiphlogistic or immunosuppressive active ingredient |
| US9949947B2 (en) | 2012-12-11 | 2018-04-24 | Sapiotec Gmbh | Delphinidin for combating melanoma cells |
| US10357464B2 (en) | 2006-09-20 | 2019-07-23 | The Board Of Regents Of The University Of Texas System | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0124071D0 (en) * | 2001-10-08 | 2001-11-28 | Kbig Ltd | Improvement in the administration of high boiling point aneasthetics |
| CA2549524A1 (en) * | 2004-01-02 | 2005-07-28 | Wisconsin Alumni Research Foundation | Encapsulation of chemical compounds in fluorous-core and fluorous-inner-shell micelles formed from semifluorinated-block or fluorinated-block copolymers |
| WO2005077337A2 (en) * | 2004-02-05 | 2005-08-25 | Baxter International Inc. | Dispersions prepared by use of self-stabilizing agents |
| CN102006903A (en) * | 2008-01-22 | 2011-04-06 | 维波真尼克斯公司 | Volatile anesthetic compositions and methods of use |
| WO2010129686A1 (en) * | 2009-05-05 | 2010-11-11 | Vapogenix, Inc. | Novel formulations of volatile anesthetics and methods of use for reducing inflammation |
| CA3049854C (en) * | 2011-06-24 | 2022-10-11 | Vapogenix, Inc. | Formulations and methods for treating dermatological disorders or diseases |
| WO2013016511A1 (en) | 2011-07-27 | 2013-01-31 | University Of Miami | Stable liquid formulations of volatile gas anesthetics |
| JP6669645B2 (en) | 2013-03-15 | 2020-03-18 | ベイポジェニックス インコーポレイテッド | Novel analgesic composition |
| JPWO2015132985A1 (en) * | 2014-03-03 | 2017-04-06 | 丸石製薬株式会社 | Sevoflurane-containing emulsion composition |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4073943A (en) * | 1974-09-11 | 1978-02-14 | Apoteksvarucentralen Vitrum Ab | Method of enhancing the administration of pharmalogically active agents |
| IL78929A0 (en) * | 1985-07-29 | 1986-09-30 | Abbott Lab | Microemulsion compositions for parenteral administration |
| JPH01226807A (en) * | 1988-03-04 | 1989-09-11 | Tsumura & Co | Fat emulsion and production thereof |
| CA2013755C (en) * | 1989-04-05 | 1993-11-30 | Simon Benita | Medicinal emulsions |
| US5916596A (en) * | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
| DE19609476A1 (en) * | 1996-03-11 | 1997-09-18 | Basf Ag | Stable parenteral administration suitable carotenoid emulsions |
| US5637625A (en) * | 1996-03-19 | 1997-06-10 | Research Triangle Pharmaceuticals Ltd. | Propofol microdroplet formulations |
-
1999
- 1999-05-27 GB GB9912446A patent/GB2350297A/en not_active Withdrawn
-
2000
- 2000-05-25 EP EP00937799A patent/EP1180014A2/en not_active Withdrawn
- 2000-05-25 CA CA002371033A patent/CA2371033A1/en not_active Abandoned
- 2000-05-25 WO PCT/US2000/014502 patent/WO2000072820A2/en not_active Ceased
- 2000-05-25 AU AU52926/00A patent/AU5292600A/en not_active Abandoned
- 2000-05-25 JP JP2000620932A patent/JP2003520769A/en active Pending
-
2005
- 2005-01-14 US US11/035,935 patent/US20050129754A1/en not_active Abandoned
Non-Patent Citations (7)
| Title |
|---|
| Anesth. Analg., vol 41, no 3, May-June 1962, PP 257-262 * |
| Anesth. Analg., vol 47, no 5, September-October 1968, pp 557-559 * |
| Anesth. Analg., vol 88, 1999, pages 671-675 * |
| Anesthesiology, vol 68, no 5, November 1985, pp 490-499 * |
| RBI Catalogue, 1999, Sigma-Aldrich Chemical Co. Ltd, page 180 * |
| Shinshu Igaku Zasshi, vol 18, no 4, 1969, pp 104-(838) to 114-(848) & Chem. Abstr. No 74:110157 * |
| The CTFA Cosmetic Ingredient Dictionary, 3rd edition, 1982 page 238 * |
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|---|---|---|---|---|
| WO2002094221A1 (en) * | 2001-05-18 | 2002-11-28 | Jupitar Pty Ltd | Emulsion and dispersion formulations and method |
| EP1558226A4 (en) * | 2002-10-11 | 2008-04-02 | Baxter Int | Method for cardioprotection and neuroprotection by intravenous administration of halogenated volatile anesthetics |
| AU2003282464B2 (en) * | 2002-10-11 | 2010-02-25 | Baxter International, Inc. | Method for cardioprotection and neuroprotection by intravenous administration of halogenated volatile anesthetics |
| US7999011B2 (en) * | 2002-10-11 | 2011-08-16 | Baxter International Inc. | Method for cardioprotection and neuroprotection by intravenous administration of halogenated volatile anesthetics |
| US10357464B2 (en) | 2006-09-20 | 2019-07-23 | The Board Of Regents Of The University Of Texas System | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
| US10799466B2 (en) | 2006-09-20 | 2020-10-13 | The Board Of Regents Of The University Of Texas System | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
| EP2345427A1 (en) * | 2010-01-14 | 2011-07-20 | SapioTec GmbH | Fluoran complex |
| WO2011086146A1 (en) * | 2010-01-14 | 2011-07-21 | Sapiotec Gmbh | Halogenated ether complex |
| US9125953B2 (en) | 2010-01-14 | 2015-09-08 | Sapiotec Gmbh | Halogenated ether complex |
| US9827394B2 (en) | 2011-09-21 | 2017-11-28 | University College Cardiff Consultants Limited | Dispersion anaesthetic device |
| US9925274B2 (en) | 2012-11-15 | 2018-03-27 | Sapiotec Gmbh | Delphinidin complex as an antiphlogistic or immunosuppressive active ingredient |
| US9949947B2 (en) | 2012-12-11 | 2018-04-24 | Sapiotec Gmbh | Delphinidin for combating melanoma cells |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9912446D0 (en) | 1999-07-28 |
| JP2003520769A (en) | 2003-07-08 |
| AU5292600A (en) | 2000-12-18 |
| WO2000072820A3 (en) | 2001-04-05 |
| EP1180014A2 (en) | 2002-02-20 |
| CA2371033A1 (en) | 2000-12-07 |
| WO2000072820A2 (en) | 2000-12-07 |
| US20050129754A1 (en) | 2005-06-16 |
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